title: Transcriptional Regulation of TMP21 by NFAT.
abstract: BACKGROUND
  TMP21 is a member of the p24 cargo protein family, which is involved in protein transport between the Golgi apparatus and ER. Alzheimer's Disease (AD) is the most common neurodegenerative disorder leading to dementia and deposition of amyloid β protein (Aβ) is the pathological feature of AD pathogenesis. Knockdown of TMP21 expression by siRNA causes a sharp increase in Aβ production; however the underlying mechanism by which TMP21 regulates Aβ generation is unknown, and human TMP21 gene expression regulation has not yet been studied.
  
  
  RESULTS
  In this report we have cloned a 3.3-kb fragment upstream of the human TMP21 gene. The transcription start site (TSS) of the human TMP21 gene was identified. A series of nested deletions of the 5' flanking region of the human TMP21 gene were subcloned into the pGL3-basic luciferase reporter plasmid. We identified the -120 to +2 region as containing the minimal sequence necessary for TMP21 gene promoter activity. Gel shift assays revealed that the human TMP21 gene promoter contains NFAT response elements. Expression of NFAT increased TMP21 gene expression and inhibition of NFAT by siRNA reduced TMP21 gene expression.
  
  
  CONCLUSIONS
  NFAT plays a very important role in the regulation of human TMP21 gene expression. This study demonstrates that the human TMP21 gene expression is transcriptionally regulated by NFAT signaling.
authors.affiliation: Department of Surgery, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 410006, China. liushengchun1968@163.com.
authors.forename: Shengchun
authors.initials: S
authors.lastname: Liu
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Kelley
authors.initials: K
authors.lastname: Bromley-Brits
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhou
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Jill
authors.initials: J
authors.lastname: Mittelholtz
authors.forename: Weihong
authors.initials: W
authors.lastname: Song